ABSTRACT The overarching goal of this application submitted in response to RFA-DA-16-015, ?Services Planning Research in the Appalachian Region to Address Adverse Health Consequences Associated with Increased Opioid Injection Drug Use?, is to examine knowledge of new HCV pharmacotherapies and willingness to engage in HCV treatment among rural HCV-positive people who inject drugs (PWID). In addition, we propose to determine the capacity of the current health care system to provide HCV treatment to PWID in Appalachian Kentucky. The ongoing HCV epidemic in the U.S. is largely driven by the increase in opioid injection (both prescription and heroin) in recent years. Kentucky has been particularly susceptible to the HCV/opioid abuse syndemic, with HCV incidence rates that lead the nation, concentrated in the rural Appalachian region. The Social Networks among Appalachian People (SNAP) study is an ongoing NIDA-funded cohort of 675 rural Appalachian drug users for which vast epidemiologic data on substance use, social networks, and infectious disease outcomes have been collected since 2008. It is clear that HCV is one of the most, if not the most, pressing issue facing rural PWID, and SNAP participants in particular. Although these increased HCV rates among PWID are highly concerning, newly approved HCV pharmacotherapies (direct-acting antivirals ? DAAs) offer revolutionary advancement over previous ribavirin/pegylated interferon-?-based treatment. The high rates of sustained virologic response among the newer DAA regimens may serve not only to cure the individual patient, but may also prevent further transmission among PWID. However, little is known about the knowledge of rural PWID around DAAs, and more importantly, whether they would even be willing to initiate treatment with these novel drugs. Further, it is not known what the capacity is to treat PWID with DAAs in rural Appalachian communities. Therefore, the specific aims are: 1) To examine knowledge of the HCV clinical course and novel DAAs among HCV-positive PWID in Appalachian Kentucky; 2) To determine willingness to engage in DAA treatment among HCV-positive PWID; and 3) To establish the capacity of local health care providers to treat HCV-positive PWID with novel DAAs, the results of which will be shared via a Stakeholder Meeting. The SNAP study team is uniquely positioned to make a significant contribution to the knowledge around the potential for HCV treatment service delivery in resource- poor Appalachian Kentucky. Further, it is highly likely these results will be generalizable to other areas in Appalachia (i.e., TN, VA, WV) with similar ongoing HCV opioid use syndemics. In addition to informing the potential capacity for HCV service delivery in the community, these data will also inform the optimal design of local HCV treatment programs that maximize DAA engagement rates among rural Appalachian PWID, ultimately reducing HCV transmission rates and the overall burden of opioid injection in Appalachian Kentucky.